Recent evidence obtained in a variety of experimental circumstances suggests that the process of glomerular ultrafiltration in mammals is subject to humoral regulation. The presence of specific receptor sites for a variety of humoral and vasoactive substances have been demonstrated in glomeruli of rats, dogs and rabbits, and recent micropuncture studies have identified the functional characteristics of these substances, which include parathormone, antidiuretic hormone, prostaglandins, angiotensin II and histamine. The recent evidence for this previously unrecognized humoral regulation of glomerular ultrafiltration also necessitates an intensive investigative effort to determine the functional roles of these substances in the altered glomerular function seen in many physiological and pathophysiological conditions, particularly when endogenous levels of these substances are elevated. Accordingly, this research project is aimed at 1) clarifying further the biological mechanisms involved in the glomerular actions of humoral substances and 2) identifying the functional roles of those substances in inducing altered glomerular function in various physiological and pathophysiological conditions. Using micropuncture techniques, preglomerular, glomerular and postglomerular pressures and flows will be measured during experimentally induced variations in glomerular function to determine the specific sites and modes of alteration of the glomerular microcirculation. To assist in the identification of the substances responsible for these alterations, a variety of specific inhibitors of hormones and biochemical messengers will be examined.